Mdn246 186.19

SIGNIFICANCE OF CXCR3 EXPRESSION IN GASTRIC
LOW-GRADE B-CELL LYMPHOMA OF MUCOSA-ASSOCIATED
HIGH-RESOLUTION GENOME WIDE-DNA PROFILING IN MARGINAL
LYMPHOID TISSUE TYPE FOR PREDICTING RESPONSIVENESS TO
A. Rinaldi1, I. Kwee1, P. M. Rancoita1, M. Ponzoni2, G. Bhagat3, U. Novak3,
H. Yamamoto1, T. Nakamura2, K. Matsuo3, M. Tajika2, H. Kawai2, N. Ohmiya4,
V.V. Murty3, S.V. Nandula3, G. Gaidano4, R. Marasca5, M. Mollejo6, F. Facchetti7,
S. Dirnhofer8, L. Baldini9, V. Gattei10, V. Canzonieri10, A. Gloghini11, J. Soulier12,
1Department of Pathology and Clinical Laboratories, Nagoya University Hospital,
C. Thieblemont12, F. Forconi13, G. Pruneri14, A. Carbone11, C. Doglioni2,
Nagoya, Japan, 2Department of Endoscopy, Aichi Cancer Center Hospital,
M.G. Tibiletti15, E. Zucca1, M.A. Piris6, R.D. Gascoyne16, R. Dalla Favera3,
Nagoya, Japan, 3Division of Epidemiology and Prevention, Aichi Cancer Center
Research Institute, Nagoya, Japan, 4Department of Gastroenteralogy, Nagoya
1 IOSI, Bellinzona, Switzerland, 2, HSR, Milan, Italy, 3 Columbia Un., NY, United
University Graduate School of Medicine, Nagoya, Japan
States, 4 A. Avogadro Univ. of Eastern Piedmont, Novara, Italy, 5 Univ. ofModena and Reggio E., Modena, Modena, Italy, 6 CNIO, Madrid, Spain, 7
Background: Gastric MALT lymphoma is a distinct low-grade lymphoma that often
Spedali Civili, Brescia, Italy, 8 Universita¨t, Basel, Switzerland, 9 Osp. Maggiore,
regresses upon Helicobacter pylori eradication. The chemokine receptor CXCR3 is
Milan, Italy, 10 CRO, Aviano, Italy, 11 INT, Milan, Italy, 12 Hop. Saint-Louis, Paris,
a candidate molecule that could influence gastric MALT lymphoma. In this study, we
France, 13 Siena University, Siena, Italy, 14 IEO, Milan, Italy, 15Varese Univ.,
aimed to elucidate the correlation between CXCR3 expression and the
clinicopathologic features of gastric MALT lymphoma, and to determine whetherCXCR3 expression was predictive of responsiveness to H. pylori eradication.
Introduction: MZL subtypes (extranodal, EMZL; nodal, NMZL; splenic, SMZL) are
Material and methods: Sixty-seven patients with gastric MALT lymphoma in a single
considered unique lymphoma subtypes. Despite the fact that general clinical
center study were treated with H. pylori eradication therapy. We evaluated the
presentations vary and specific translocations are present only in EMZL, a high-
correlation of CXCR3 expression with response to H. pylori eradication therapy by
resolution genetic analysis of these disorders has not been done.
logistic regression stratified according to potential confounders.
Material and Methods: DNA from frozen biopsies analyzed with Affymetrix Human
Results: Immunohistochemical analysis revealed that 28 of 67 cases (42%) were
Mapping 250K arrays. Gene expression profiling with U133 plus 2.0 was performed on
positive for CXCR3 expression. CXCR3 expression was significantly more prevalent in
those without H. pylori infection, advanced stage disease, and in those with API2-
Results: 38 out of 138 already collected samples have been analyzed so far: 10 NMZL,
MALT1 fusion. In overall analysis, those with CXCR3 expression showed a significantly
10 EMZ, 18 SMZL. All subtypes had recurrent gains of chromosome 3, 12q13.3-q15,
increased risk of non-responsiveness to H. pylori eradication therapy (OR = 28.6; 95%
14q32.33 and losses of 7q11.23, 19q13.2-pter, 19q13.2. Recurrent gains were
CI, 5.70 to 143.4) compared to those without CXCR3 expression. This higher risk was
identified in chromosome 18 (NMZL and SMZL), 1q21.3-q32.1 (EMZL), 8p23, 18q23,
observed consistently regardless of sex, API2-MALT1 fusion, H. pylori infection, and
20q13.33 and 21q22.3 (SMZL). Recurrent losses were identified in 7q32.1-q32.3,
14q24.2-q32.13 (SMZL), 9q34.3, 11q13.1, 16p13.3, 16p13.11 (NMZL and EMZL),
Conclusions: We showed that CXCR3 expression was an independent predictive factor
12q24.11, and 17p13.3 (NMZL). Recurrent regions of copy-neutral LOH, suggestive of
for non-responsiveness to H. pylori eradication therapy in patients with gastric MALT
uniparental disomy (UPD), were observed at 10q26.13 (SMZL), 2p21 (EMZL), and
6p21.32-p21.33 (NMZL). However, only 1/38 cases had UPD stretches longer than 5Mb, and this was different from what we have observed in other B-cell tumors (>150),which show UPD in as many as 50% of the cases.
Conclusions: In the first series of MZL cases analyzed, in addition to known disease-specific aberrations, novel lesions have been identified. Complete data on over 150
MICRORNA EXPRESSION IN NODAL AND EXTRANODAL
C. Mandrup1, A. Petersen1, A.D. Hoejfeldt1, H.F. Thomsen1, J. Madsen1,
PROGNOSTIC SIGNIFICANCE OF PRIMARY EXTRANODAL
J. Dahlgaard1, P. Johansen2, A. Bukh1, K. Dybkaer1, H.E. Johnsen1
DIFFUSE LARGE B-CELL LYMPHOMA (DLBCL) IN PATIENTS
1Department of Hematology, Aalborg Hospital, Aarhus University Hospital,
Aalborg, Denmark, 2Pathological Institute, Aalborg Hospital, Aarhus UniversityHospital, Aalborg, Denmark
D. Hui1, B. Proctor1, J. Donaldson1, T. Shenkier1, P. Hoskins1, R. Klasa1,K. Savage1, R. Gascoyne2, J.M. Connors1, L.L. Sehn1
Introduction: The aim of this project was to analyse microRNA (miRNA) expression
1Medical Oncology, Vancouver Cancer Centre, Vancouver, BC, Canada,
in nodal and extranodal diffuse large B-cell lymphoma (DLBCL). Manifestation at
2Pathology, Vancouver Cancer Centre, Vancouver, BC, Canada
diagnosis may be nodal and/or extranodal. At present, there are no knowndeterminants for none of the manifestations, and no way to predict the potential
Background: Previous studies in the pre-rituximab era have identified important
progression from nodal to extranodal disease. miRNA are small regulatory RNA
clinical differences between nodal and primary extranodal DLBCL. We have examined
molecules, which function to repress/cleave sequence complementary mRNA targets.
the prognostic significance of primary extranodal DLBCL in the post-rituximab era.
Abnormalities in miRNA genetics and expression are known to affect initiation and
Methods: Using the Lymphoid Cancer DATAbase of the British Columbia Cancer
development of human diseases, and miRNAs are anticipated to play a direct role in
Agency, all patients ‡18 years of age diagnosed with DLBCL between January 1999 and
oncogenesis and differentiation. Therefore, we hypothesise miRNA to be important for
May 2006 and treated with an R-CHOP regimen were included for analysis. Patients
both characterization and progression of DLBCL.
were excluded if they were HIV positive, presented with disease in the testicular or
Materials and Methods: A global miRNA screen (Exiqon miRCURYTM LNA Array) of
central nervous system, or had known coincident indolent lymphoma. Primary
50 snap-frozen DLBCL (40 nodal, 10 extranodal), identified differentially expressed
extranodal DLBCL was defined as disease confined to one or more localized extranodal
miRNAs between the two manifestations. Subsets of miRNA profiles are pending to be
sites, with no or minimal nearby nodal involvement.
validated by Taqman RT PCR assays in the original 50 snap frozen samples, 50 highly
Results: 513 patients were identified with the following characteristics: median age 62 y
selected FFPE samples and 10 new snap-frozen samples.
(range 19-93), male 59.1%, stage III/IV 53.8%, elevated LDH 49.5%, and performance
Results: It was possible to distinguish between the nodal and extranodal manifestations
status ‡2 38.2%. While 350 (68.2%) had at least some degree of extranodal
with the global miRNA screen (e.g. mir143, mir432, mir127, and mir195).
involvement, only 133 (25.9%) had primary extranodal DLBCL. Among patients with
Differentially expressed miRNA target genes were predicted by target prediction
primary extranodal disease, 70 (52.6%), 37 (27.8%) and 26 (19.6%) had 1, 2 and ‡3
software (Targetscan and Miranda). Statistically software (GOstat) to annotate target
extranodal sites, respectively. The most commonly involved extranodal sites included
gene ontology revealed several prominent ontologies like proliferation (e.g. WNT5a,
bone (33.1%), soft tissue (28.6%), stomach (15.0%), intestine (12.8%), and sinus
MAPK), and cell adhesion (several members of the PCDHA family) to be differentially
(10.5%). Thirty-two percent, 20%, 0% and 48% of patients with primary extranodal
affected in the two manifestations. Interestingly many miRNA had the wnt pathway as
DLBCL had stage I, II, III, and IV, respectively. This is in contrast to 11%, 34%, 26%
and 29% for the nodal DLBCL group. Primary extranodal DLBCL was less commonly
Conclusion: The two manifestations were distinct from each other with respect to
associated with an elevated LDH (37.6% vs. 53.7%, p=0.001). With a median follow-up
miRNA expression; this difference may provide extra information about this
of 2.8 years, no significant difference in overall survival was detected between primary
heterogeneously disease, and lead to further studies of the differentiated miRNAs to
extranodal and nodal DLBCL analyzed either as a group or by individual stages.
examine the step wise progression from nodal to extranodal manifestation.
Furthermore, no specific primary extranodal site confers a worse prognosis.ª The Author 2008. Published by Oxford University Press on behalf of the European Society for Medical Oncology.All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org
Conclusion: In the post-rituximab era, the previously identified survival difference in
THE ROLE OF RADIOTHERAPY, PERFORMANCE STATUS, AND
primary extranodal DLBCL is no longer observed in this large cohort.
DOSAGE OF METHOTREXATE ACCORDING TO THEAGEIN PRIMARYCNS LYMPHOMA PATIENTS RECEIVED UPFRONT HIGH DOSEMETHOTREXATE BASED CHEMOTHERAPY
IPI AND FLIPI ARE NOT APPLICABLE IN PATIENTS WITH MALT
J. Kim,1 W. Kim,2 C. Suh,3 D. Yang,4 H. Eom,5 S. Bang,6 S. Oh,7 S. Lee,8 H. Kim,9J. Park,10 J. Won,11 S. Yoon,12 C Kim13 and Korean Society of Hematology
1Int.Med.I, Med.University, Vienna, Austria
1Department of Internal Medicine, Yonsei University College of Medicine, Seoul,Korea; 2Samsung Medical Center;3 Asan Medical Center; 4Chonnam National
Background: The prognostic value of the international prognostic index (IPI) and the
University; 5National Cancer Center; 6Seoul National University Bundang
follicular lymphoma international prognostic index (FLIPI) has widely been
Hospital; 7Dong-A University; 8Dankook University; 9Hallym University; 10Gil
demonstrated in diffuse large B-cell lymphoma and follicular lymphoma. No attempts
Medical Center; 11Soonchunhyang University; 12Seoul National University;13
to assess their applicability in MALT lymphoma have been performed so far.
Patients and Methods: 153 patients MALT-lymphoma were analysed. Parameters ofboth IPI [age>60 years, extranodal involvement ‡2, elevated LDH, PS ‡2, stage ‡3] and
Introduction: We evaluated the role of RTx after CTx, initial performance status, and
FLIPI [age>60 years, elevated LDH, stage ‡3, nodal involvement ‡5, hemoglobin £12g/
total cumulated dosage of MTX according to the age in PCNSL.
dl] were assessed and correlated with relapse and time to relapse as markers of clinical
Material and methods: 188 immunocompetent PCNSL patients (median age 50 years)
course. Statistical analysis was done with SPSS 14.0. Partial correlation was assessed
receiving CTx containing high-dose MTX (>1 g/m2) were selected at 17 institutions.
with the Pearson coefficient (CF) and reassessed with multiple regression analysis.
Results: Age£50 years, ECOG<2 and RTx after CTx were significant prognostic factors
Estimated time to relapse curves were calculated with the Kaplan Meier method and
predicting improved OS. Multivariate analysis indicated that ECOG<2 (P=0.044,
tested for significant differences with the Log-Rank test.
OR=1.76) and RTx after CTx (P=0.001, OR=2.69) were significant prognostic factors
Results: According to the IPI 109 patients (71%) were classifed as low risk, 21(14%) as
for prediction of OS. Planned treatment was CTx alone (group1) in 64 (34%, median
low-intermediate, 16(10%) as high-intermediate, and 7(5%) as high risk. FLIPI
age 61 years) patients and CTx followed by RTx (group2) in 124 (66%, median age 46
identified 100 patients (68%) at low, 33(22%) at intermediate and 14(10%) at high
years). Among the patients£50, group2 patients survived longer than group1 (3-years
risk. After a median follow up time of 58 months, 132 patients are alive and 60 have
OS; 79% vs 56%, P=0.03). Other risk factors were not statistically significant. Adding
relapsed (median time to relapse: 40 months). Neither IPI (CF:0.06, p=0.395) nor
cytarabine to MTX based CTx, combination MTX based CTx, and adding intrathecal
FLIPI (CF:0.06, p=0.4) correlated with relapse or time to relapse. Univariate analysis
CTx did not improved OS in the PCNSL patients£50. Multivariate analysis indicated
demonstrated stage, extragastric disease, autoimmune disease, trisomy 18 and
that higher total cumulated dosage of MTX (‡5 g/m2) (P=0.041) was significant
multifocal disease as significantly correlated with relapse, while trisomy 18, extragastric
prognostic factor for prediction of OS in the PCNSL patients£50. Among the
disease and multifocal disease were correlated with shorter time to relapse. Multiple
patients>50, group 2 patients also survived longer than group 1 (3-years OS; 73% vs
regression analysis identified only extragastric and mutifocal disease as predictive
39%, P=0.01). ECOG<2 was significant prognostic factor for prediction of OS
factors of relapse (p=0.08; p=0.011). The time of follow-up was also significantly
(P=0.03). Other factors including total dose of MTX were not significant.
Conclusions: In the younger PCNSL patients, CTx followed by RTx improved survival
Conclusion: IPI and FLIPI are not relevant for predicting the clinical course of MALT-
and sufficient total cumulated dosage of MTX or combination MTX based CTx
lymphoma. Multiple regression analysis has demonstrated a significant correlation
regimen might improve the OS. In elderly PCNSL patients, initial ECOG was the
between follow-up time and relapse as well as extragastric MALT lymphoma and
relapse and time to relapse. In view of this, prolonged follow-up is warranted inpatients with MALT lymphoma, especially of extragastric origin.
CANDIDATE GENE EXPRESSION PROFILING BY REAL-TIME
PCR IN FORMALIN FIXED AND PARAFFINE EMBEDDED (FFPE)SAMPLES OF PRIMARY CNS LYMPHOMAS (PCNSL)
THE NF-kB PATHWAY AS A TARGET TO INCREASE
APOPTOSIS IN PRIMARY MEDIASTINAL B-CELL LYMPHOMA
L. Fischer1, M. Hummel2, A. Korfel1, D. Lenze2, A. Ehlers2, P. Martus3, M. Weller4,
(PMBL): STUDIES WITH SMALL MOLECULE IKK INHIBITOR ML120B,
BORTEZOMIB (BTZ), CYCLOPHOSPHAMIDE (CY) AND
1Hematology, Oncology & Transfusion Medicine, Charite´ Campus Benjamin
Franklin, Berlin, Germany, 2Institute of Pathology, Charite´ Campus BenjaminFranklin, Berlin, Germany, 3Institute of Biometrics and Clinical Epidemiology,
I. Waxman1, C. van de Ven1, J. Ayello1, N. Day1, M.S. Cairo2
Charite´ Campus Mitte, Berlin, Germany, 4Dept. of Neurology, University Hospital
1Pediatrics, Columbia University, New York, United States, 2Pediatrics,
Pathology & Medicine, Columbia University, New York, United States
Background: The evaluation of biological prognostic factors in PCNSL has yielded
PMBL is a rare subtype of diffuse large B-cell lymphoma (DLBCL) with a significantly
contradictory results thus far. In this study we evaluated the feasibility of PCR based
lower EFS than other identically treated DLBCLs (Lones/Cairo, JCO, 2000).
gene expression profiling using FFPE samples from immunocompetent PCNSL
Upregulation of anti-apoptotic NF-kB pathway genes occurs in PMBL (Rosenwald, J
patients. Expression of candidate genes with prognostic impact in nodal diffuse-large
Exp Med, 2003). We studied the effect of 2 NF-kB pathway blocking agents, BTZ and
B-cell lymphoma (DLBCL) was correlated to survival in PCNSL.
ML120B (supplied by Millennium Pharm, MA), and Cy on apoptosis in PMBL to
Methods and Material: FFPE tumor samples from PCNSL patients obtained by open
identify strategies to increase cell death.
resection were collected, and samples with a tumor content of >70% were subjected
PMBL line Karpas-1106P was incubated with ML120B (10 lg/ml), BTZ (5 ng/ml),
to RNA analysis. RNA was extracted using commercially available kits and reverse
Cy (1.25 mg/ml), ML120B+BTZ or ML120B+Cy for 24h. Percentage of cells induced to
transcribed with sequence specific primers. The expression of BCL2, BCL6, CCL3,
undergo apoptosis was measured using Annexin V-FITC. DLBCL line SUDHL-6, with
CCND2, HGAL, FN1, MYC, MUM1, LRMP, PLAU and IL4 was measured and
low expression of NF-kB genes, was used for comparison. For combination studies,
normalized to the mean expression of four endogenous control genes: GAPDH, GUSB,
comparisons were made between single and combination therapy samples run
PKG1, SDHA. Overall survival (OAS) was determined using the Kaplan-Meier method
and the prognostic impact of gene expression using the Cox model.
Significant increases in PMBL apoptosis occurred after incubation with each agent
Results: Samples from 42 patients with PCNSL, all histologically DLBCL, and a median
(ML120B: 4.0%±1.13, p<.0005; BTZ: 5.25%±1.43, p<.02; Cy: 4.8%±1.05, p=.006).
age of 63 (26-87) years were evaluated. All patients have been initially treated with
Significant increases occurred in SUDHL-6 after treatment with BTZ (46.42%±6.52,
high-dose (4g/m2) methotrexate, followed by a consolidating and rescue whole brain
p<.0001), but not after treatment with Cy or ML120B. ML120B+BTZ led to
irradiation in 10 patients each. RNA could be extracted from all samples.
a synergistic increase in apoptosis in PMBL when compared to ML120B single agent
Electrophoretic quality control identified considerable RNA degradation. Except for
therapy (17-fold [1700%] increase, p<.01) and BTZ single agent therapy (4-fold
IL4, the expression of all genes could be measured in 40 samples (95%). The median
[400%] increase, p<.01), respectively. In contrast, ML120B+BTZ did not cause an
OAS of all patients was 29 (0.5-69) months. None of the genes examined had
increase in apoptosis in SUDHL-6, with no significant change in apoptosis found after
a statistically significant influence on survival, however, a trend towards longer survival
treatment with ML120B+BTZ vs. BTZ alone (BTZ: 25.92%±1.32, ML120B+BTZ:
was seen for the overexpression of FN1 (HR 1.35, p=0.09), and PLAU (HR 1.27,
24.62%±5.19, difference in increase between BTZ & BTZ+ML120B: 1.29%, p=NS).
p=0.17), and the reduced expression of CCND2 (HR 0.87, p=0.19). Patients <60 years
ML120B+Cy in PMBL led to an additive increase in apoptosis (ML120B: 5.49%±1.74,
had a median OAS of 32 months compared to 24 months for older patients (p=0.3).
Cy: 6.57%±1.16, ML120B+Cy: 13.82%±2.3, p<.03).
Karnofsky index had no impact on survival.
ML120B and BTZ both increase apoptosis in PMBL, possibly by blocking the NF-kB
Conclusion: FFPE material is suitable for RT-PCR based analysis of genes with possible
pathway at different points. This may explain why combination therapy with
prognostic impact in PCNSL. However, the results obtained yielded no statistical
ML120B+BTZ is synergistic, while the effect of ML120B+Cy is additive. Studies to
significance. This might be due to their inability to predict clinical outcome in PCNSL
assess expression of NF-kB genes in PMBL after single and combination therapy are
or to the relatively small cohort investigated.
ADDITION OF RITUXIMAB TO CHOP GREATLY IMPROVES THE
1Department of Internal Medicine, Seoul National University Hospital, Cancer
OUTCOME OF PATIENTS WITH PRIMARY MEDIASTINAL LARGE
Research Institute, Seoul National University College of Medicine, Seoul, Korea,
Republic of, 2Department of Ophthalmology, Seoul National University Hospital,Seoul National University College of Medicine, Seoul, Korea, Republic of,
T. P. Vassilakopoulos1, G. Pangalis1, Z. Galani1, S. Sachanas1, A. Katsigiannis2,
3Department of Pathology, Seoul National University Hospital, Seoul National
E. Vrakidou3, C. Poziopoulos4, N. Constantinou5, P. Repoussis6, M. Dimopoulou1,
University College of Medicine, Seoul, Korea, Republic of
S. Kokoris1, E. Michali1, E. Dimitriadou1, S. Masouridis1, M. Siakantaris1,C. Kalpadakis1, M. Kyrtsonis1, P. Panayiotidis1, P. Poussou2, M. Angelopoulou1
Introduction: Despite a variable association between ocular adnexal MALT lymphoma
1Dept of Hematology, University of Athens, Laikon University Hospital, Athens,
and Chlamydia psittaci (Cp) infection, high rate of Cp-positivity was observed in
Greece, 23rd Dept of Internal Medicine, University of Athens, Athens, Greece,
Korean patients with ocular adnexal MALT lymphoma. Additionally, there are
3Hematology Dpt, Hygeia Hospital, Athens, Greece, 4Hematology Dpt, General
conflicting results regarding Cp-eradicating doxycycline. This study was undertaken to
Army Hospital, Athens, Greece, 5Hematology Dpt, Theageneion Hospital,
analyze the efficacy of blind doxycycline in localized ocular adnexal MALT lymphoma.
Salonica, Greece, 6Hematology Dpt, METAXA Hospital, Athens, Greece
Materials and methods: Twenty-one patients diagnosed as extranodal marginal zoneB-cell lymphoma of MALT type were analyzed. Doxycycline at a dose of 200mg daily
Background: Rituximab-CHOP (RCHOP) is superior to CHOP, being the new
for 3 weeks was given to unselected patients with ocular adnexal MALT lymphoma as
standard of care for patients with diffuse LBCL. In PMLBCL, which usually affects
a first-line (n=17) or second-line (n=4) between 2005 and 2007. Lymphoma response
young patients, several investigators prefer the use of MACOP-B or even front-line
and progression-free survival (PFS) were analyzed.
high dose therapy with autologous stem cell support (HDT-ASCT). However, the role
Results: Patients’ median age was 47 with a male-to-female ratio of 0.6:1. Doxycycline
of RCHOP in PMLBCL is not well established yet.
was well-tolerated in ocular adnexal lymphoma patients, of whom only one
Patients and Methods: 82 patients with PMLBCL were treated in 6 centers (1994-
discontinued doxycycline after one week due to dizziness. Seven patients (33%)
2007): 39 consecutive patients who received RCHOP±Radiotherapy (RT) were
achieved lymphoma regression (2 complete responses and 5 minimal responses), while
compared to 43 consecutive historical controls, who had received CHOP±RT.
remaining 14 patients showed stable disease. In the first-line group, two-year PFS rate
Results: The median age of the patients was 31 years (17-82) and 53/82 (65%) were
was 65% and median PFS was 22.2 months. In patients with disease progression,
females. All individual IPI parameters and B-symptoms were balanced between the two
subsequent chemotherapy or radiotherapy induced complete response in 4 out of 6
groups. The median follow-up of currently alive patients was 33 and 88 months for
patients. However, in the second-line group, two-year PFS rate was 50% and median
patients treated with RCHOP±RT and CHOP±RT respectively. All failures occurred
PFS was 10.5 months. Overall, 13 (62%) of 21 patients remained progression-free after
within 22 months from diagnosis. The 3-year failure free survival (FFS) was 81±6% vs
doxycycline therapy after a median follow-up of 18 months.
53±8% for patients who received RCHOP±RTvsCHOP±RT (p=0.006). The 3-year
Conclusions: Doxycycline alone is effective in localized ocular adnexal MALT
event free survival (EFS) was 79±7% vs 51±8% (p=0.007). The 3-year overall survival
lymphoma as a first-line treatment. Future efforts should be directed toward
was 92±5% vs 67±7% (p=0.009), while the 3-year lymphoma specific survival (LSS)
determining the Cp status and finding a marker associated with doxycycline resistance.
Conclusions: RCHOP±RT provided very good results in PMLBCL: Early progressions
CHLAMYDOPHILA PSITTACI (CP) IS VIABLE AND INFECTIOUS
were minimized, long-term FFS exceeded 80%, and only 3 lymphoma-related deaths
IN THE CONJUNCTIVA AND PERIPHERAL BLOOD OF PATIENTS
were recorded so far in 39 patients after a median follow-up of 33 months. Patients
WITH OCULAR ADNEXAL MALT LYMPHOMA (OAML): RESULTS OF A
treated with RCHOP had significantly higher FFS, EFS, OS, and LSS, when compared
to CHOP-treated historical controls. Based on these results we continue to treatPMLBCL patients with RCHOP±RT, avoiding more intensive strategies.
A.J. Ferreri1, R. Dolcetti2, G.P. Dognini3, L. Malabarba3, N. Vicari4, E. Pasini2,
NO BENEFIT OF ADDING RITUXIMAB TO CHOP REGIMEN IN
M. Ponzoni3, M. Cangi3, L. Pecciarini3, A. Giordano Resti3, C. Doglioni3,
PATIENTS WITH PRIMARY EXTRANODAL TYPE OF DIFFUSE LARGE
Dept. of Oncology, San Raffaele H Scientific Institute, Milan, Italy, 2 Centro di
Riferimento Oncologico, Aviano, Italy, 3 San Raffaele H Scientific Institute, Milan,
G. Jang1, S. Kim1, D. Lee1, S. Kim1, H. Kim2, C. Suh1
Italy, 4 National Reference Laboratory for Animal Chlamydioses, IZSLER, Pavia,
1Internal medicine, Asan Medical Center/University of Ulsan college of medicine,
Seoul, Korea, Republic of, 2Internal medicine, Hallym University Medical Center,Anyang, Korea, Republic of
Background: Some lymphomas are linked to specific bacterial infections.Confirmation of these associations by bacteria isolation from patients’ (pts) samples
Background: The addition of rituximab to CHOP chemotherapy (R-CHOP) has
(second Koch’s postulate) has been achieved for H. pylori, but not for other lymphoma-
significantly improved clinical outcome for patients (pts) with diffuse large B-cell
related bacteria. OAML is linked to Cpinfection, but the viability and infectivity of this
lymphoma (DLBCL). However, new predictors of response to R-CHOP have not been
microorganism in OAML pts has not been investigated yet.
established. We performed a retrospective analysis to evaluate the clinical impact of
Methods: A single-center prospective trial was conducted to assess the prevalence of Cp
R-CHOP and tried to identify clinical predictors to get better benefit from R-CHOP
infection in 20 OAML pts and 42 healthy blood donors referred to our Institution in
compared with CHOP in pts with DLBCL.
a 6-month period, and to define whether the Cp DNA and antigens previously detected
Material and methods: Using the population-based cancer registry for non-Hodgkin’s
in OAML pts correspond to a viable and infectious microorganism. The presence of Cp
lymphoma of Asan Medical Center, we identified eligible 177 pts who were newly
on conjunctival swabs and peripheral blood mononuclear cells (PBMC) of pts and
diagnosed with CD20-positive DLBCL and treated with CHOP (n=82) or R-CHOP
donors was assessed by TETR-PCR and in vitro cultural methods. The presence of Cp
(n=95) as first-line therapy from January 2001 to November 2005. We especially
was assessed also in lymphoma tissue.
subgrouped all pts into either primary extranodal lymphoma (PENL, n=72) or nodal
Results: Donors were more commonly young males living in urban areas, whereas
lymphoma (NL, n=105) according to the main origin of disease. PENL was defined as
OAML pts frequently reported a history of chronic conjunctivitis and prolonged
lymphoma which had either no or minor nodal involvement along with a clinically
contact with household animals (85% vs. 38% of donors; p=0.00001). Cp was detected
dominant extranodal component after routine staging procedures. Response rate,
in lymphoma tissue of 15 (75%) pts. Cp DNA was detected in conjunctival swabs and/
event-free survival (EFS) and overall survival (OS) were compared between CHOP and
or PBMC from 10 (50%) OAML patients and in PBMC from one (2%) donor
R-CHOP group. To identify clinical predictors, subgroup analysis was performed with
(p=0.01). Viability and infectivity of Cp, demonstrated by growth in cell cultures, were
log-rank test and Cox regression model.
confirmed in conjunctival swabs and/or PBMC from 5 (25%) OAML pts, but not in
Results: Complete response rate and overall response rate were higher in R-CHOP
than CHOP group though it didn’t meet statistical significance between two groups
Conclusions: This prospective trial demonstrates, for the first time, that Cp is viable
(79% vs 69%, p=0.16 and 97% vs 90%, p=0.07). Two-year EFS and OS rates were
and infectious in conjunctival swabs and/or PBMC of OAML pts. Cp infection is
higher in R-CHOP group (82% vs 74%, p=0.22 and 83% vs 77%, p=0.23). In subgroup
common in OAML pts and exceptional in blood donors. Epidemiological features in
analysis, pts with NL had a prominent survival benefit from R-CHOP over CHOP
OAML pts are consistent with increased risk of Cp exposure.
(p=0.02 in EFS and p=0.03 in OS) but pts with PENL did not (p=0.37 in EFS andp=0.61 in OS). Other factors such as age, ECOG performance status, stage, LDH and
VALUE OF 18F-FDG-PET SCAN IN THE DIAGNOSIS AND
IPI showed no difference for survival outcome according to treatment regimen.
STAGING OF OCULAR ADNEXAL LYMPHOMA (OAL): A LARGE
Conclusions: R-CHOP regimen showed improved outcome in pts with DLBCL
compared with CHOP, but pts with PENL had no benefit from addition of rituximabto CHOP chemotherapy. These pts might need other treatment strategy.
M. Zanni1, G. Moulin-Romsee2, V. Servois3, P. Validire1, C. Plancher4,L. Lumbroso-Le Rouic5, R. Dendale6, A. Vincent-Salomon7, M. Be´namor2,B. Asselain4, L. Desjardins8, C. Precupanu1, C. Le´vy8, D. Decaudin1
ANTI-TUMOR ACTIVITY OF BLIND DOXYCYCLINE IN
1Clinical Hematology, Institut Curie, Paris, France, 2Nuclear Medicine, Institut
LOCALIZED OCULAR ADNEXAL MUCOSA-ASSOCIATED LYMPHOID
Curie, Paris, France, 3Radiology, Institut Curie, Paris, France, 4Biostatistics,
Institut Curie, Paris, France, 5Ophthalmology, Institut Curie, Paris, France,6Radiotherapy, Institut Curie, Paris, France, 7Tumor Biology, Institut Curie, Paris,
K. Kim1, T. Kim1, S. Lee1, D. Kim1, S. Khwarg2, C. Kim3, D. Heo1
France, 8Ophthalmology, Institut Curie, Paris, France
Introduction: Fluorine 18 deoxyglucose Positron Emission Tomography (PET) is
CGH/FISH and data from expression profiling of microdissected lymphoma cells of
largely used in the staging of non-Hodgkin’s lymphomas (NHL), but very few studies
a cDNA chip containing 2300 genes. Feature class selection for isolation of new
have focused on its role in the initial staging of patients (pts) presenting ocular adnexal
prognostic genes was performed. TP53 protein and proliferation index were evaluated
lymphoma (OAL). The aim of this study was therefore to evaluate the role of FDG-PET
in the diagnosis of ophthalmologic lymphomatous localizations.
Results: In 7/22 lymphomas a deletion (5/22) or a mutation (5/22) of TP53 was
Patients and Methods: A retrospective review of all imaging records, including
detected. When compared to the numbers of genomic aberrations no correlation
computed tomography (CT), magnetic resonance imaging (MRI), and 18F-FDG-PET
regarding a higher number of aberrations was detected. More than two cytogenetic
of all OAL pts treated at the Institut Curie between 2003 and 2007 was performed. The
aberrations were correlated with significantly shorter mean survival, while TP53 failed
ability of PET studies to detect lymphomatous ophthalmologic involvement was then
as a predictor. Genomic profiling of deleted and mutated TP53 lymphomas revealed
compared with other staging explorations.
four differentially expressed genes in both groups (false discovery rates 0.003 and 0.006,
Results: Thirty-one OAL pts were included in the study. Pathological review according
respectively). These were PTPRD, which is an analogue of CD45; CCNG2, a cell cycle
to the WHO classification showed 22 low-grade lymphoma pts (71%) in whom 15
regulator; MAPK12, a major transducer of extracellular signals; and CCL7, a monocyte
MALT lymphoma (48%) and 9 high-grade NHL in whom 6 diffuse large B-cell
chemotactic protein. Nuclear TP53 protein accumulation was generally low in the
lymphoma (19%). Ophthalmologic sites were intra-orbital in 20 pts (65%) in whom 3
deleted cases while TP53 was heterogeneously detected in the mutated lymphomas
with bilateral localizations and conjunctival in 14 pts (45%) in whom 3 with bilateral
ranging from 5% to 95% positive lymphoma cells.
localizations. All patients had FDG PET and orbital MRI assessment at diagnosis in 21
Conclusions: A core group of four differentially expressed genes was defined that
cases and orbital CT in 28 pts. 18F-FDG PET positive lesions were correlated to
might be influenced by mutations/deletions of TP53. Furthermore, feature selection for
pathological sites detected by MRI in 12/21 pts (57%) and 6 pts had negative FDG PET
class selection of complete remission revealed a group of differentially expressed genes
but positive MRI;18F-FDG PET positivity was correlated to pathological sites detected
by CT in 17/28 pts (61%). At last, concordances between PET/MRI and PET/CT were71% (p=0.06) and 79% (p=0.02), respectively. The sensitivity of FDG PET, MRI, andCT were 77%, 87%, and 80%, respectively.
CLINICOPATHOLOGICAL FEATURES AND OUTCOME OF
Conclusions: As anticipated, this study shows that 18F-FDG-PET has a lower sensitivity
STAGE I GASTRIC MALT LYMPHOMA TREATED WITH
than MRI to detect ophthalmologic lymphomatous localizations.
G. Pinotti1, A. Stathis2, C. Capella1, I. Proserpio1, C. Chini1, F. Bertoni2,
PROGNOSTIC VALUE EXPRESSION OF CD38 IN PRIMARY
1Oncology and Pathology, Ospedale di Circolo and University of Insubria,Varese, Italy, 2IOSI, Oncology Institute of Southern Switzerland, Bellinzona,
N. Kondratieva1, I. Poddubnaya1, E. Sholohova1, E. Osmanov1, O. Moskalenko1,
Switzerland, 3ICP, Institute of Pathology, Locarno, Switzerland
N. Tupitsyn11Chemotherapy of Haemoblastosis, Cancer Research Center after N.N. Blokhin,
Background: The efficacy of Helicobacter Pylori (HP) eradication in localized gastric
MALT lymphoma is well established with remission rates between 60-100% of cases.
However, only scanty information is available about long-term follow-up of antibiotic-
Background: B-cell lymphomas of mucosa-associated lymphoid tissue (MALT)
represent a clinically, morphologically and biologically heterogeneous group. There is
Methods: 100 patients (pts) with stage I gastric MALT lymphoma were treated initially
no information about prognostic value expression of CD38 in MALT-lymphomas. The
with anti-HP eradication regimens comprising antibiotics in association with proton-
aim of our study was to evaluate the level of expression CD38 and outcome of patients
pump inhibitors. Follow-up endoscopies with multiple biopses were carried out at 6
with primary gastric MALT-lymphomas.
Materials: We have studied immunohistological features of 34 pts with primary gastric
Results: Median age at diagnosis was 64 years. All patients presented with
MALT-lymphomas stage I (Lugano) treated between 1995-2005. There were 15 (44%)
gastrointestinal symptoms (mainly abdominal pain/dyspepsia) but no B symptoms
males and 19 (56%) females. Age of patients (pts) ranged 21-79 years (median 58). The
were observed. HP was detected by histology in 80%. Lymphoma was most often
median of follow-up was 36 months (range 3-96). Two groups were identified. First
localized in the antrum (30%), was multifocal in 19%, associated with gastritis in 54%
group (3 pts) - expression of CD38 on lymphoma cells, second group (31 pts)
and with ulcers in 29% of cases. After antibiotics, HP was eradicated in all positive
- expression of CD38 on plasmocytes. Last group may be subdivided in two groups: 12
patients (19 of them after a second line of antibiotics). Symptoms disappeared and
(39%) pts with low level of CD38+ plasma cells (group A) and 19 (61%) pts with
macroscopic findings improved in almost all patients. Lymphoma regression was
intensive CD38+ plasma cell reaction (group B). Helicobacter pylori infection status
achieved in 78 of 97 evaluable patients (80%, 95% CI.: 71-88%) with histological
was assessed as positive in 31 cases. Antibacterial treatment was performed for 31
complete remission (CR) in 66 (Wotherspoon’s score 0-2) and partial remission
patients with expression of CD38 on plasmacytes. Three patients with expression of
(score 3) in 12 pts. A multifocal presentation was significantly (p=0.04) associated with
CD38 on lymphoma cells were treated by chemotherapy.
lower CR rate (47%) in comparison with fundus+ body (65%) and antrum (82%). The
Results: Results were analysed in group A and B. Complete remission was observed in
median follow-up time was 6.5 years; 34 of the 78 responders showed continuous
93%. Eight (27%) pts had relapses: 6 relapses were mainly in group B, only 2 in group
histological remission, while 33 had histological score fluctuations (from 0-4) and
A. The 2-years disease free survival was 86% in pts with low level of CD38+ plasma cell,
11 pts had a frank lymphoma relapse (2 with high-grade trasformation). The 5-year
53% in pts with intensive CD38+ plasma cell reaction (not significant).
and 10-year overall survivall rates were 91% (95% CI, 83-95) and 82% (95% CI, 69-90),
Conclusions: The present results show that the cases of primary gastric MALT-
lymphomas stage I (Lugano) with different level of CD38+ plasma cell in lymphoma
Conclusions: Hp eradication therapy resulted in CR in the majority of cases, with
tissue have various clinical outcome, long-term survival and risk for relapses. These
a significantly higher CR rate in tumors of the distal stomach. Long-term clinical
results could be taken into account for the individual treatment for patients with
disease control was achieved in most cases. Incidence of histologic transformation
primary gastric MALT-lymphomas with initial high CD38+ plasma cell proportion.
seems lower in gastric MALT lymphoma than in other low-grade lymphomas.
Future studies of expression CD38 may be helpful for assessment of prognosis forpatients with gastric MALT-lymphomas.
INTRAVASCULAR LARGE B-CELL LYMPHOMA (IVLBCL):
INTERNATIONAL CONSENSUS ON DIAGNOSTIC AND THERAPEUTIC
INSTABILITITY AND EXPRESSION PROFILES IN 22 DIFFUSE LARGEB CELL LYMPHOMAS OF THE GASTROINTESTINAL (GI)-TRACT
M. Ponzoni1, A.J. Ferreri1, E. Campo1, G.P. Dognini1, F. Facchetti1, T. Kinoshita1,L. Mazzucchelli1, T. Yoshino1, T. Murase1, M. Seto1, K. Shimada1, S.A. Pileri1,
T.F. Barth1, T. Zenz2, H.A. Kestler3, M. Buchholz4, T. Gress5, S. Stilgenbauer6,
C. Doglioni1, E. Zucca1, F. Cavalli1, S. Nakamura1
1Pathology, San Raffaele Scientific Institute, Milano, Italy, On Behalf of
1Institute of Pathology, University of Ulm, Ulm, Germany, 2University of Ulm,
International Intravascular Lymphoma Study Group
Internal Medicine III, Ulm, Germany, 3Neural Information Processing, Universityof Ulm, Ulm, Germany, 4Gastroenterology, Philipps University, Marburg,
Background: IVLBCL is a rare form of diffuse large B-cell lymphoma with preferential
Marburg, Germany, 5Gastroenterology, Philipps University, Marburg, Marburg,
intravascular growth of malignant lymphocytes, aggressive behavior, and usually fatal
Germany, 6Internal Medicine III, University of Ulm, Ulm, Germany
course. IVLBCL often affects elderly patients with poor PS, elevated LDH serum levels,anemia, and B-symptoms, with possible differences in clinical presentation between
Introduction: TP53 is regarded as one of the main tumor suppressors. Deletion and/or
cases diagnosed in Western Countries and Japan. Many characteristics of IVLBCL are
mutations of TP53 are believed to cause genomic instability and neoplastic
poorly known and may be broader than those currently described.
Methods: On behalf of the International Extranodal Lymphoma Study Group,
Material and methods: Twenty-two diffuse large B cell lymphomas of the GI-tract
clinicians and pathologists interested in IVLBCL, coming from Western and Eastern
were analyzed for deletion and mutations of the TP53 by FISH and sequencing. The
countries, joined to reach a consensus on the most urgent unresolved issues in IVLBCL:
data were correlated with a database that integrated genomic abberrations detected by
to this end, a representative group of IVLBCL cases coming from Western countries
and Japan were collectively analyzed. IVLBCL features were proposed both under
Objective and Patients: To evaluate the usefulness of rituximab in IVL, we
clinical and pathologic standpoints.
retrospectively analyzed 106 patients (59 men, 47 women) with IVL who received
Results: the consensus indicated that: IVLBCL have additional morphological criteria
chemotherapy either with rituximab (R-chemo, n=49) or without rituximab (Chemo,
including definition of affected vessels, cell size (somewhat smaller cell may occur),
n=57) between 1994 and 2007 in Japan. Median patient age was 67 years (range, 34 to
peculiar sites of involvement (kidney, spleen and liver), and immunophenotype (in
84 years). IPI was H-I/H in 97% of patients.
particular CD5 expression); difference in clinical forms of IVLBCL is driven more by
Results: Complete response rate was higher for R-chemo (82%) than for Chemo (51%,
the presence of haemophagocytosis rather than geographical origin of patients;
P=0.001). Median duration of follow-up for surviving patients was 18 months (range, 1
‘‘cutaneous variant’’, PS, stage, and therapeutic modality are independent prognostic
to 95 months). Progression-free survival (PFS) and overall survival (OS) rates at 2 years
variables; therapy is improved by anthracycline-based chemotherapy plus rituximab,
after diagnosis were significantly higher for R-chemo (PFS: 56%; OS: 66%) than for
CNS prophylaxis and consolidation with high-dose chemotherapy supported by
Chemo (PFS: 27%, P=0.001; OS: 46%, P=0.01). Multivariate analysis revealed use of
autologous stem cell transplant, mostly in high-risk and young patients.
rituximab was favorably associated with PFS (HR, 0.45; 95% CI, 0.25 to 0.80; P=0.006)
Conclusion: IVLBCL is a peculiar type of diffuse large B-cell lymphoma under
and OS (HR, 0.42; 95% CI, 0.21 to 0.85; P=0.016). Adverse events related to rituximab
pathological, immunophenotypic, clinical and therapeutical standpoints. An
infusion were observed in 14 of 49 patients (29%). Grade 3 hypoxia due to rituximab
international prospective protocol, aimed to study both therapeutical and biological
infusion was observed in one of 49 patients (2%). Treatment-related death was
features of this disease is currently being designed.
observed in 3 patients (6%) with R-chemo and 5 patients (9%) with Chemo. Twelve of
For more information, please contact: ponzoni.maurilio@hsr.it,
49 patients (24%) in the R-chemo group and 31 of 57 patients (54%) in the Chemo
group had died as of final follow-up. In the R-chemo group, 4 patients each died ofprogressive disease (PD) and relapsed disease (RD), respectively. In the Chemo group,15 patients and 11 patients died of PD and RD, respectively.
Conclusion: Our data suggest improved clinical outcomes for patients with IVL in the
rituximab era without significant increase in toxicities. Future prospective studies of
PATIENTS WITH INTRAVASCULAR LARGE B-CELL LYMPHOMA (IVL)
rituximab-containing chemotherapies are warranted.
G.P. Dognini1, M. Ponzoni2, O. Bairey3, C. Montalba`n4, A. Szomor5, L. Uziel6,J. Seymour7, A. Ambrosetti8, M. Martelli9, G. Rossi10, M. Federico11,A. Candoni12, A. De Renzo13, M. Piris14, E. Zucca15, C. Doglioni2, A.J. Ferreri1
PRIMARY TONSIL NON-HODGKIN’S LYMPHOMA, CLINICAL
1Dept. of Oncology, San Raffaele H Scientific Institute, Milan, Italy, 2Pathology
CHARACTERISTICS, PROGNOSIS AND SURVIVAL ANALYSIS
Unit, San Raffaele H Scientific Institute, Milan, Italy, 3Div. of Hematology, RabinMedical Center, Beilinson Hospital, Petah Tiqwa, Israel, 4Servicio de Medicina
Interna, Hospital Ramo´n y Cajal, Madrid, Spain, 5First Dept. Medicine, Univ. of
Medical Oncology, Cancer Institute/Hospital, Chinese Academy of Medical
Pecs, Pecs, Hungary, 6Hematology Unit, Ospedale San Paolo, Milan, Italy,
Sciences (CAMS) & Peking Union Medical College (PUMC), Beijing, China
7Australasian Leukaemia and Lymphoma Group, and Univ. of Melbourne,Melbourne, Australia, 8Hematology Unit, Policlinico G.B. Rossi, Verona, Italy,
Objectives: This study aimed to analysis the clinical characteristics, prognostic factors
9Div. of Hematology, Universita` La Sapienza, Rome, Italy, 10Hematology Unit,
and treatment outcome of Chinese patients with primary non-Hodgkin’s lymphoma
Spedali Civili, Brescia, Italy, 11Hematology Unit, H Policlinico, Modena, Italy,
12Hematology Unit, Policlinico Universitario, Udine, Italy, 13Div. of Hematology,
Methods: From May 1990 to March 2007, 106 patients with previously untreated NHL
Universita` Federico II, Naples, Italy, 14Div. of Pathology, Centro Nacional de
of tonsil were retrospectively reviewed. The median age was 49 years. In theall 106
Investigaciones Oncolo`gicas, Madrid, Spain, 15Div. of Medical Oncology, Ist.
patients, 68.9% diagnosed of diffuse large-B-cell lymphoma (DLBCL), 11.3% of
Oncologico Svizzera Italiana, Bellinzona, Switzerland
peripheral-T-cell lymphoma (PTCL) and 7.5% of indolent B-cell lymphoma. Ninety-eight (92.5%) patients presented with stage I and II disease. Majority of patients
Background: The addition of rituximab to anthracycline-containing chemotherapy
(69.8%) received combined chemoradiotherapy and 17.9% treated by radiotherapy
has significantly improved outcome in patients (pts) with diffuse large B-cell
alone as initial treatment. The predominant chemotherapy regimens were CHOP and
lymphomas. The impact of this monoclonal antibody in IVL, a rare variant of diffuse
BACOP, and radiotherapy dose range between 40-50Gy.
large B-cell lymphoma characterised by the growth of neoplastic cells into small blood
Results: After a median follow-up of 51 months, the estimate 5-year overall survival
vessels was recently explored in a large series of Japanese pts, while experience in IVL
(OS) and disease free survival (DFS) were 82% and 68%, respectively. Significant
pts diagnosed in Western Countries is limited to a few case reports
prognostic factors included: advanced disease and locally extra-nodal involvement.
Methods: The impact of the addition of rituximab was evaluated in 28 pts affected by
Other prognostic factors, such as age older than 60 years, B symptoms, bulky disease,
CD20+ IVL eligible for CHOP/CHOP-like regimen: 8 pts were treated with rituximab
T cell lymphoma and treatment modalities as chemoradiotherapy or radiotherapy
+chemotherapy (R-CT) and 20 with chemotherapy alone (CT).
alone did not show significant results on outcome.
Results: Median age was 67 yrs (range 39-86; 15 males). 75% of pts had an IPI‡3.
Conclusions: Survival for the patients with primary tonsil NHL is optimal as most of
B symptoms, PS‡3, increased LDH levels, and stage IV were respectively observed in
the patients have stage I or II diseases. Diffuse large-B-cell lymphoma is the most
78%, 41%, 88%, and 71% of cases. Skin (44%), CNS (30%) and bone marrow (30%)
common pathological subtype. Multivariate analysis by Cox regression shows that
were the most common sites. Laboratory tests revealed: anemia (78%), leucopenia
advanced stage, primary refractory disease and locally extra-nodal infiltration are
(30%), thrombocytopenia (37%), and increased LDH (88%). No significant
differences between R-CT and CT groups were observed. Overall, 18 (64%) pts
Keywards: tonsil neoplasms; Non-Hodgkin’s lymphoma; chemotherapy;
achieved complete remission (CR), and 2 partial response with an early progression
(PD), 6 (21%) experienced a PD, and 2, both in CT group, died of toxicity. NoteworthyCR was obtained in 100% of R-CT versus 50% of CT pts (p=0.03); the addition ofrituximab was related to CRR. At a median f-up of 14 mo, all 8 R-CT pts are alive and
DIFFUSE LARGE B-CELL LYMPHOMAS OF THE WALDEYER’S
relapse free; at a median f-up of 71 mo, only 7 CT pts are alive and disease-free. The
RING: A CLINICO-PATHOLOGICAL STUDY OF 209 PATIENTS FROM
3-yr EFS was 35% in CT group and 100% for R-CT pts (p<0.0001); the 3-yr OS was
THE GROUPE D’ETUDE DES LYMPHOMES DE L’ADULTE (GELA)
39% and 100%, respectively (p<0.0001).Conclusions: the addition of rituximab to anthracycline-based chemotherapy
Laurence de Leval1,5, C. Bonnet2,5, C. Copie-Bergman4,5, L. Seidel3, M. Baia4,
significantly improves outcome in IVL pts diagnosed in Western Countries. A
J. Brie`re4, T. Molina5, B. Fabiani5, B. Falini5, C. Gisselbrecht5, H. Thilly5, A. Albert3,
confirmatory international prospective trials is warranted.
On behalf of the International Extranodal Lymphoma Study Group (IELSG)
Departments of Pathology1 Hematology2, Biostatistics3, CHU Sart-Tilman,Lie`ge, Belgium; Department of Pathology, Hoˆpital Henri Mondor4, Cre´teil,France; GELA group5
A RETROSPECTIVE ANALYSIS OF RITUXIMAB-CONTAINING
CHEMOTHERAPIES FOR INTRAVASCULAR LARGE B-CELL
DLBCLs are markedly heterogeneous, and their biological features may vary according
to the primary site of disease. The WR is the second most common site of extranodalinvolvement by DLBCL.
K. Matsue1, K. Shimada1, K. Yamamoto1, T. Murase1, N. Ichikawa1,
We analyzed 209 adult patients with de novo DLBCL presenting in the WR
M. Okamoto1, N. Niitsu1, H. Kosugi1, N. Tsukamoto1, H. Miwa1, H. Asaoku1,
consecutively included in the GELA trials (1993-2004) (M/F: 1,8; mean age 59 yrs; 81%
A. Kikuchi1, M. Matsumoto1, Y. Saburi1, Y. Masaki1, M. Kashimura1, T. Yoshida1,
stages I-II) and treated with anthracyclin-based polychemotherapy. Morphology and
M. Yamaguchi1, S. Nakamura1, T. Naoe1, T. Kinoshita1
immunophenotype were analyzed and correlated to the clinical features. FISH assays
1Intravascular Large B-cell Lymphoma Study Group, IVLSG, Nagoya, Japan
with split-signal DNA probes were performed on a subset of cases. Survival andoutcome were compared to a matched cohort primary nodal DLBCL patients.
Background: Intravascular large B-cell lymphoma (IVL) is a rare subtype of extranodal
By morphology, 55% of WR DLBCLs were centroblastic, 39% centroblastic-
diffuse large B-cell lymphoma (DLBCL) with poor prognosis. Addition of rituximab to
polymorphous, 3% immunoblastic, and 3% unclassifiable. Among large biopsy
CHOP and CHOP-like regimens has been found to improve the outcome of DLBCL.
specimens (n=79), 53% had a prominent or minor nodular pattern and 47% were
However, the efficacy of rituximab in IVL remains unclear.
purely diffuse. The prevalence of antigen expression was: bcl2: 105/189 (60%); CD10:
75/178 (42%); bcl6: 40/76 (53%); mum-1:40/109 (37%). The immunophenotype
modalities used so far. MTh also appears to be important for consolidation or even
of 136 cases was GC-like in 60% and non-GC-like in 40%. In multivariate analysis,
GC-like cases correlated with better OS (p=0.014). Rearrangement of BCL-2, BCL6 andc-MYC loci were found by FISH in 3/42, 9/35 and 3/41 cases. For 144 paired WR/nodal cases, the CR rate was significantly better for WR patients (p=0.01) but the 5-yOS and EFS rates (79,7% and 70,9% in WR patients, and 76,7% and 66,7% in nodalpatients) did not significantly differ. For 109 paired patients with no adverse prognosticfactor of the aa IPI, primary WR localization was associated with a higher 5-y EFS
ACTIVITY OF BORTEZOMIB IN MALT LYMPHOMAS: A IELSG
(78,5% vs. 71,2%; p=0,029) and 0S (84,7% vs. 79,8%; p=0,047) rates.
In conclusion, WR DLBCLs frequently have a partially follicular pattern of growth,
and a GC-like phenotype. In DLBCL patients with an aa IPI = 0, the WR localization
A. Conconi1, A. Lopez-Guillermo2, G. Martinelli3, L. Rigacci4, U. Vitolo5,
appears to confer a better outcome than primary nodal involvement.
P.L. Zinzani6, A. Ferreri7, S. Luminari8, M. Martelli9, F. Cavalli10, E. Zucca101Hematology, ASO Maggiore della Carita`, Universita` Amedeo Avogadro,Novara, Italy, 2Hematology, Hospital Clinic, University of Barcelona, IDIBAPS,
RITUXIMAB MONOTHERAPY IS THE TREATMENT OF CHOICE
Barcelona, Spain, 3Hematology, European Institute of Oncology, Milan, Italy,4
Hematology, Careggi Hospital and University of Florence, Florence, Italy,
5Hematology, ASO San Giovanni Battista, Turin, Italy, 6Institute of Oncology and
C. Kalpadakis1, G.A. Pangalis2, T.P. Vassilakopoulos2, M.N. Dimopoulou2,
Hematology L. and A. Sera`gnoli, University of Bologna, Bologna, Italy, 7Onco-
M. Kyrtsonis2, P. Korkolopoulou2, F. Kontopidou2, M. Siakantaris2,
hematology, San Raffaele Institute, Milan, Italy, 8Oncology and Hematology,
E. Dimitriadou2, P. Panayiotidis2, H. Papadaki1, M. Angelopoulou2
University of Modena and Reggio Emilia, Modena, Italy, 9Hematology, University
1Dept of Hematology, University of Crete, University Hospital of Heraklion,
of Rome, Rome, Italy, 10Oncology Institute of Southern Switzerland, IOSI,
Heraklion, Heraklion, Greece, 2Dept of Hematology, University of Athens, Laikon
The International Extranodal Lymphoma Study Group (IELSG) is coordinating
Introduction: There is no standard therapy for SMZL. Splenectomy has been
a phase II trial aimed to assess the antitumor activity and safety of bortezomib in
considered as the first line treatment although it may carry significant complications.
patients (pts) with relapsed or refractory extranodal marginal zone B-cell lymphoma of
We present our results on the efficacy of Rituximab as a first line treatment in SMZL
MALT-type. Bortezomib 1.3 mg/m2 is administered on days 1, 4, 8, and 11 of a 21-day
cycle, for up to 6 cycles. Response and progression are determined by InternationalWorkshop Criteria. As of January 2008, 25 pts have been enrolled in the study: among
Patients and methods: We analysed 24 pts with SMZL diagnosed in our Dpt between
the 21 pts in whom the data are available, 12 (57%) patients were male, median age was
2003 and 2007. All pts received Rituximab at a dose of 375mg/m2/week for 6
63 years (range, 38–81). At time of enrolment, the Ann Arbor stages distribution was
consecutive weeks at a median time of 1,5 mo after diagnosis. Maintenance therapy
the following: stage I=5 pts (24%), stage II=5 pts (24%), stage IV=11 (52%). In 11 pts
(MTh) was given as one dose of 375mg/m2 Rituximab every 2 mos for one year. Pts’
primary gastric localization was present, in 5 cases primary skin, in 2 cases primary
median age was 57 years (range 48-78). At diagnosis all pts had splenomegaly and bone
subcutaneous, moreover a primary lung, orbit, muscle localization was reported in 1 pt
marrow infiltration. Response criteria were defined as follows: CR: complete clinical,
each. All patients had ECOG PS=0; in 3 cases (14%) elevated serum LDH was reported.
morphologic and immunophenotypic remission, unconfirmed CR: clinical and
More than 1 site of extranodal localization was present in 5 pts (24%). Median number
laboratory CR without bone marrow evaluation, PR: 50% improvement of clinical and
of prior therapies was 2 (range, 1–3). Median follow-up was 17 months. Eleven pts were
assessed for response at the end of treatment plan: 3 pts had a CR (27%); 4 a PR (37%)
Results: Overall response was 100%. All pts had complete resolution of splenomegaly
and 3 SD (27%) and 1 a PD (9%). Four additional pts, with ongoing therapies, have
at a median time of 5 weeks (median 2-15) after treatment initiation along with
been evaluated after the first two courses of therapy: one pt achieved a CR, 1 pt a PR,
restoration to normal of their blood counts at a median time of 4 weeks (1-44). 17 pts
1 pt a SD and in 1 a PD was observed. Significant duration of response was observed
(71%) achieved a CR, 4 an unconfirmed CR (17%), and 3 (12%) a PR. Among the CR’s
among the 4 pts in CR, ranging from 18 to 22 months and in most cases still ongoing.
5 pts had also a molecular remission. 20 pts underwent MTh, while 4 did not. 12/20 pts
The safety profile of bortezomib is similar to that observed in multiple myeloma and
have already completed MTh. 10/12 pts who completed MTh sustained their response
other subtypes of non-Hodgkin lymphoma. The most relevant grade 3 or higher
and 2 pts achieved an improvement of response. 2 relapses were recorded at a median
adverse events were peripheral neuropathy and fatigue. Three deaths, non-related to
time of 21,5 mos. Median follow up time for the entire series is 29 mos (range 6-91). No
treatment, were observed during the early follow up. These preliminary results suggest
that bortezomib is active and safe in relapsed or refractory MALT lymphomas and
Conclusions: The present study demonstrates that Rituximab is a highly effective
encourage us to complete the studies accrual.
treatment for SMZL. It confers better response rates in relation to other treatment
Disclosure: Research Funding: Johnson & Johnson partially supported the trial.